A novel role for carbon monoxide as a potent regulator of intracellular [Ca.sup.2+] and nitric oxide in rat pancreatic acinar cells

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Date: Dec. 2014
Publisher: American Physiological Society
Document Type: Author abstract; Report
Length: 273 words

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Abstract :

Carbon monoxide (CO) is known as an essential gaseous messenger that regulates a wide array of physiological and pathological processes, similar to nitric oxide (NO) and hydrogen sulfide. The aim of the present study was to elucidate the potential role of CO in [Ca.sup.2+] homeostasis and to explore the underlying mechanisms in pancreatic acinar cells. The exogenous application of a CO-releasing molecule dose-dependently increased intracellular [Ca.sup.2+] concentration ([[Ca.sup.2+].sub.i]). A heme oxygenase (HO) inducer increased [[[Ca.sup.2+]].sub.i] in a concentration-dependent manner, and the increase was diminished by an HO inhibitor. The CO-induced [[[Ca.sup.2+]].sup.i] increase persisted in the absence of extracellular [Ca.sup.2+], indicating that [Ca.sup.2+] release is the initial source for the increase. The inhibition of G protein, phospholipase C (PLC), and inositol 1,4,5-trisphosphate ([IP.sub.3]) receptor diminished the CO-induced [[[Ca.sup.2+]].sub.i] increase. CO upregulated endothelial nitric oxide synthase (eNOS) expression and stimulated NO production, and NOS inhibitor, calmodulin inhibitor, or the absence of extracellular [Ca.sup.2+] eliminated the latter response. Blocking the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway abolished CO-induced NO production. Pretreatment with an NOS inhibitor, NO scavenger, or soluble guanylate cyclase inhibitor, did not affect the CO-induced [[[Ca.sup.2+]].sub.i] increase, indicating that NO, soluble guanylate cyclase, and cyclic guanosine 5'-monophosphate are not involved in the CO-induced [[[Ca.sup.2+].sub.i] increase. CO inhibited the secretory responses to CCK-octapeptide or carbachol. We conclude that CO acts as a regulator not only for [[[Ca.sup.2+]].sub.i] homeostasis via a PLC-[IP.sub.3]-[IP.sub.3] receptor cascade but also for NO production via the calmodulin and PI3K-Akt/PKB pathway, and both CO and NO interact. Moreover, CO may provide potential therapy to ameliorate acute pancreatitis by inhibiting amylase secretion. carbon monoxide; [Ca.sup.2+]; nitric oxide; pancreatic acinar cells doi: 10.1152/ajpcell.00252.2014

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Gale Document Number: GALE|A397453169